Uncovering the Phenomenon Behind Cancer Cell Size and Drug Resistance
Scientists have found out that cancer cells can either become smaller or bigger, in order to handle difficulties in their surroundings such as drug treatments.
Scientists from The Institute of Cancer Research in London used a combination of chemistry and math to figure out why some cancer cells are bigger than others. Their discovery could help create new treatments.
A new study published in the journal Science Advances suggests that smaller cancer cells might be more affected by chemotherapy and drugs compared to larger ones. To reach this conclusion, researchers studied millions of skin cancer cells through advanced image analysis and looked at DNA and protein levels.
Skin cancer melanoma is caused by two different types of genetic mutations. Around 60% of cases are linked to the BRAF gene mutation, while 20-30% of cases are caused by an NRAS mutation. Scientists decided to study the size and shape of skin cancer cells that had either one of these two mutations. To do so, they used mathematics algorithms and looked at a lot of data which focused on specific DNA and proteins.
BRAF-mutant cancer cells were much smaller than NRAS-mutant cancer cells. And the drug resistant NRAS cells were even bigger in size. Scientists found out that the smaller cancer cells seemed to be more able to handle more damage on their DNA because these small cells had a lot of proteins which help repair the DNA like PARP, BRCA1 and ATM1 proteins.
Scientists think that people with ICR are at higher risk of being affected by medicines called PARP inhibitors. These medicines block a protein that helps fix damaged DNA, especially when someone is taking another medicine to harm the DNA.
The bigger cancer cells with an NRAS mutation had damaged DNA that kept getting worse and worse, instead of being fixed. Because these cells didn’t need the same DNA repair machinery, drugs such as chemotherapy and PARP inhibitors probably won’t have much of an effect on them.
Scientists think that bigger cells may react better to treatments like immunotherapy because they have more mutations, making them look different from the body. To find out if this is true, experts are doing tests and experiments. They also believe BRAF and NRAS mutations impact cell size by changing the amount of a protein named CCND1. This protein helps control the division and growth of cells as well as their overall structure.
This research was about how skin cancer cells change in size and how this affects the way we treat them. Scientists think this same thing could happen with other types of cancer, like breast cancer, and now they are trying to figure out if it happens with head and neck cancers too.
When scientists looked into how cancer cell size affects the disease, they found out that by looking at the size of a cancer cell we can predict more accurately which treatments would be most helpful. We might even be able to use existing drugs to change the size of cancer cells so that other treatments like immunotherapy and radiotherapy work better!
A science professor, Professor Chris Bakal from The Institute of Cancer Research in London, conducted a study which showed that changes in certain genes and proteins can cause an organized shifting of the size of cancer cells. This shift in size either makes cancer cells shrink or grow bigger to help them repair DNA damage and make them resistant against some treatments.
Our research could be really useful for medical diagnosis. By looking at the size of a cell, doctors can tell if treatment will work or not. In the future, Artificial Intelligence (AI) might even help predict which treatments are best by quickly assessing cell size. We believe this discovery could also lead to new treatments like drugs that target proteins that control cell size.
Professor Kristian Helin, who is the Chief Executive of The Institute of Cancer Research, London said: “This study found a connection between changes in skin cancer cells’ genetics and their size. We think that these changes could be used to predict how someone’s cancer might respond to treatment. It’s incredible that this may also be true for other types of cancers such as breast, head and neck cancers”.
This study was funded by The Institute of Cancer Research. It is called “Characterization of proteome-size scaling by integrative omics reveals mechanisms of proliferation control in cancer” and it was written by Ian Jones, Lucas Dent, Tomoaki Higo, Theodoros Roumeliotis, Maria Arias Garcia, Hansa Shree, Jyoti Choudhary, Malin Pedersen and Chris Bakal. It was published on the 25th of January in 2023 in Science Advances with the DOI (Digital Object Identifier) 10.1126/sciadv.add0636. It looks at how different cancer cells spread and ways to stop them.
